Coronary heart disease is the leading cause of death worldwide, accounting for 3.8 million deaths in men and 3.4 million deaths in women annually. As the population grows older and comorbidities (e.g., obesity and metabolic syndrome) become more prevalent, as in recent years, the enormous public health burden caused by ischemic heart disease is likely to increase even further (reviewed in Yellon et al, N Engl J Med, 2007; 357: 1121-1135).
Coronary heart disease refers to the failure of coronary circulation to provide adequate blood supply to cardiac muscle and surrounding tissue. The most common cause of coronary heart disease is the accumulation of atheromatous plaques (i.e., fatty deposits) within the walls of coronary arteries. Occlusion of a coronary artery limits blood flow to the heart, leads to ischemia of the myocardial cells (i.e., cell starvation secondary to a lack of oxygen) and may result in myocardial cell death, which is called myocardial infarction (MI) or acute myocardial infarction (AMI)—commonly known as a heart attack. AMI is the leading cause of death in both Europe and the United States, and remains a frequent (more than 1.5 million new cases per year in the United States) and disabling (leading to heart failure) disease. Infarct size is a major determinant of myocardial functional recovery and mortality after AMI. Currently, the most effective way to limit infarct size is to reperfuse the jeopardized myocardium as soon as possible with the use of coronary angioplasty or thrombolysis and to prevent reocclusion of the coronary artery with the use of antiplatelet therapy. Reperfusion, or restoration of blood flow to the ischemic myocardium, is achieved with thrombolytic therapy that dissolves the thrombus or through dilatation of the occluded artery by percutaneous coronary angioplasty. Reperfusion is necessary for the salvage of myocardial cells and cardiac function in general. However, reperfusion initiates a cascade of events that leads to “reperfusion injury”. This also occurs following recovery from cardioplegic arrest of the heart during bypass surgery. Reperfusion injury is characterized by arrhythmias, endothelial dysfunction leading to the no-reflow phenomenon and myocardial stunning (reversible loss of myocardial contractility).
Reperfusion injury culminates in apoptotic death of cardiac cells that were viable immediately before myocardial reperfusion. The involvement of a highly-regulated form of cell death during myocardial ischemia/reperfusion may lead to novel therapeutic interventions in the reperfusion phase. However, the apoptosis signalling pathways that are involved during myocardial ischemia/reperfusion have not yet been fully delineated in vivo.
Finding new treatments for inhibiting apoptosis (i.e., “programmed cell death”), and in particular for treating myocardial infarction and reperfusion injury, thus constitutes a real challenge to protect cardiac function and to save lives.